Galanin inhibits acetylcholine release from rat cerebral cortex via a pertussis toxin sensitive Gi protein

Galanin has been implicated in various physiological functions including memory, feeding and pain perception. Using rat cerebral cortical slices and synaptosome preparations incubated with [H-3]choline in Kreb's-Ringer solution, galanin was shown to inhibit both spontaneous and K+-stimulated [H-3]ACh release in a concentration-related manner [EC50 = 35 nM]. The galanin-mediated inhibition on spontaneous and K+-stimulated [H-3]ACh release was respectively regulated by pertussis toxin-sensitive G(alpha i3) and G(alpha i1). These suggest that galanin is a negative modulator of cortical cholinergic function and most probably acting on presynaptic cholinergic terminals. Although galantide blocked the galanin-mediated inhibitory effect on [H-3]ACh release, it mimicked galanin in blocking K+-stimulated [H-3]ACh release, indicating that galantide may have a more complicated pharmacology than being a galanin receptor antagonist. In addition, we demonstrate that galanin and beta-amyloid peptide(1-42) synergistically attenuated K+-evoked [H-3]ACh release from synaptosomes prepared from rat cerebral cortex. Since galanin is increased in Alzheimer's disease brain, our results suggest that galanin may be involved in cholinergic dysfunctions that occur in Alzheimer's disease.